Affinage

SYNGAP1

Ras/Rap GTPase-activating protein SynGAP · UniProt Q96PV0

Length
1343 aa
Mass
148.3 kDa
Annotated
2026-04-28
100 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SYNGAP1 encodes a brain-enriched, dual Ras/Rap GTPase-activating protein that serves as a master regulator of excitatory synapse development, postsynaptic signaling, and synaptic plasticity. SynGAP is concentrated at the postsynaptic density through liquid-liquid phase separation of its α1 isoform with PSD-95, physically competing with AMPA receptor–TARP complexes for PSD-95 PDZ domain occupancy; CaMKII phosphorylation during LTP triggers rapid SynGAP dispersion from the PSD, relieving tonic inhibition of Ras–ERK signaling and enabling AMPAR insertion and spine enlargement (PMID:25569349, PMID:38422154, PMID:32579114). SynGAP's catalytic GAP activity is differentially regulated by CaMKII (favoring Rap1 inactivation), CDK5 (favoring HRas inactivation), PLK2, ROCK, and O-GlcNAcylation, while its structural scaffolding role—separable from catalytic function—is the principal determinant of seizure susceptibility (PMID:25533468, PMID:35637289, PMID:40294267). Heterozygous loss-of-function SYNGAP1 mutations cause intellectual disability and epilepsy by accelerating dendritic spine maturation and synaptogenesis during a postnatal critical period through both synaptic and non-synaptic mechanisms including disrupted radial glia division and cortical lamination (PMID:23141534, PMID:37946050, PMID:39111306).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1998 High

    The initial molecular identity question—what is SynGAP and how does it connect to synaptic signaling—was answered by showing it is a Ras-GAP that physically couples to the NMDA receptor complex via PSD-95 PDZ domains, placing a GTPase regulatory module directly at excitatory synapses.

    Evidence Co-immunoprecipitation, GST pulldown, and in vitro GTPase assays in brain lysates and recombinant systems

    PMID:9581761 PMID:9620694

    Open questions at the time
    • Whether SynGAP acts on Rap GTPases in addition to Ras was not yet tested
    • In vivo functional relevance not established
  2. 1998 High

    The question of how synaptic activity regulates SynGAP was first addressed by demonstrating that CaMKII phosphorylation inhibits its Ras-GAP activity, predicting that NMDA receptor activation disinhibits Ras–MAPK signaling.

    Evidence In vitro kinase and GTPase assays with recombinant SynGAP and CaMKII

    PMID:9620694

    Open questions at the time
    • Phosphorylation sites not mapped
    • Direction of effect on GAP activity was later revised by more detailed reconstitution (PMID:14970204)
  3. 2001 Medium

    Alternative splicing was shown to generate functionally distinct SynGAP isoforms: the β isoform lacks PSD-95 binding and instead associates with non-phosphorylated CaMKIIα, establishing isoform-specific scaffolding interactions.

    Evidence cDNA cloning, co-immunoprecipitation with PSD-95 and CaMKII, subcellular fractionation

    PMID:11278737

    Open questions at the time
    • Functional consequences of β-specific CaMKII binding not tested
    • No electrophysiological or morphological characterization of individual isoforms
  4. 2002 High

    Genetic evidence established that SynGAP functions in vivo as a tonic brake on ERK/MAPK signaling and is required for hippocampal LTP and spatial learning, validating the biochemical model in intact circuits.

    Evidence Heterozygous null mouse with hippocampal LTP recordings, ERK2 phosphorylation, and behavioral tests

    PMID:12427827

    Open questions at the time
    • Whether LTP defect is due to Ras-GAP activity, scaffold function, or both was unknown
    • Homozygous lethality precluded full loss-of-function analysis in adults
  5. 2004 High

    Detailed phosphosite mapping and revised biochemical characterization showed that CaMKII phosphorylation at four C-terminal sites actually increases SynGAP's Ras-GAP activity by 70–95%, and that SynGAP participates in a MUPP1-containing multiprotein complex that bidirectionally regulates AMPAR trafficking.

    Evidence Mass spectrometry, site-directed mutagenesis, in vitro GTPase assays, siRNA knockdown, and electrophysiology in neurons

    PMID:14970204 PMID:15312654 PMID:15470153

    Open questions at the time
    • Rap-GAP activity mechanism not structurally characterized
    • Relative contribution of GAP activity versus scaffolding to spine phenotype unresolved
  6. 2006 High

    Bidirectional manipulation established that SynGAP controls synaptic AMPAR content and silent synapse number through both ERK and p38 MAPK pathways, solidifying its role as a gatekeeper of excitatory transmission strength.

    Evidence Overexpression, siRNA knockdown, and KO combined with mEPSC recordings and surface AMPAR immunostaining

    PMID:16537406

    Open questions at the time
    • Whether regulation is direct or requires intermediary effectors for AMPAR insertion was unclear
  7. 2008 High

    Structural determination of the C2-GAP domain revealed that the C2 domain is essential for Rap-GAP activity, providing the first atomic-level mechanism for SynGAP's dual Ras/Rap specificity, while in vivo studies linked SynGAP to Rac–cofilin–actin cytoskeletal regulation.

    Evidence Crystal structure of C2-GAP, in vitro GTPase assays with truncations, and Ras/Rac-GTP pulldowns in heterozygous KO mice

    PMID:18323856 PMID:19074040

    Open questions at the time
    • Full-length SynGAP structure not available
    • How Rac regulation relates to Ras/Rap-GAP activity unclear
  8. 2012 High

    A developmental critical period was defined: SynGAP haploinsufficiency causes premature spine maturation and hippocampal hyperexcitability specifically during early postnatal development, with permanent cognitive consequences, establishing SynGAP as a developmental brake on circuit maturation.

    Evidence Temporal genetic manipulation in heterozygous KO mice with spine morphology, excitability recordings, and behavioral analysis

    PMID:23141534

    Open questions at the time
    • Molecular mechanism linking SynGAP loss to premature maturation not defined
    • Non-synaptic developmental roles not yet explored
  9. 2012 High

    Isoform-specific electrophysiology revealed that α1 and α2 C-terminal isoforms exert opposing effects on synaptic strength, demonstrating that alternative splicing generates functionally antagonistic variants from a single gene.

    Evidence Isoform-specific overexpression in hippocampal neurons with mEPSC recordings

    PMID:22692543

    Open questions at the time
    • Mechanism underlying opposing effects of α1 versus α2 not identified
    • In vivo isoform-specific contributions to plasticity untested
  10. 2014 High

    The kinase-specificity question was resolved: CaMKII preferentially enhances Rap1-GAP activity while CDK5 preferentially enhances HRas-GAP activity, providing a mechanism by which different upstream signals can selectively modulate SynGAP's GTPase substrate specificity.

    Evidence In vitro kinase assays with recombinant SynGAP, mass spectrometry, mutagenesis, and phospho-detection in NMDA-stimulated neurons

    PMID:25533468

    Open questions at the time
    • Whether kinase-specific substrate switching occurs in intact synapses during plasticity untested
    • Combinatorial phosphorylation logic not fully explored
  11. 2015 High

    Live imaging during LTP resolved the spatiotemporal mechanism: CaMKII phosphorylation causes rapid SynGAP dispersion from spines, and the degree of dispersion predicts maintenance of spine enlargement, establishing a direct causal link between SynGAP dynamics and structural plasticity.

    Evidence Live-cell imaging of fluorescently tagged SynGAP during LTP induction with CaMKII inhibition

    PMID:25569349

    Open questions at the time
    • Whether dispersion reflects dissolution of phase-separated condensates was not tested
    • Downstream effectors linking dispersion to AMPAR insertion not fully mapped
  12. 2016 High

    Quantitative binding studies showed SynGAP-α1 occupies ~15% of PSD-95 PDZ domains and that CaMKII/PLK2 phosphorylation reduces binding affinity severalfold, while cell-type-specific KO demonstrated SynGAP functions in GABAergic interneurons for perisomatic inhibitory connectivity and cortical gamma oscillations.

    Evidence ITC binding measurements, quantitative PSD proteomics from heterozygous mice, conditional KO in MGE-derived interneurons with electrophysiology and EEG

    PMID:27623146 PMID:27827368

    Open questions at the time
    • Whether PDZ occupancy competition is the primary mechanism for AMPAR regulation in vivo was not distinguished from GAP activity effects
    • Interneuron-specific downstream signaling pathways unknown
  13. 2018 High

    PLK2 was identified as a third kinase that phosphorylates SynGAP, with combinatorial PLK2+CDK5 phosphorylation producing additive increases in HRas-GAP and novel Rap2-GAP activity not seen with either kinase alone, revealing emergent substrate specificity from multi-kinase integration.

    Evidence In vitro kinase assays with recombinant SynGAP, PLK2, CDK5, and GTPase activity assays for HRas/Rap1/Rap2

    PMID:30049443

    Open questions at the time
    • In vivo relevance of combinatorial phosphorylation untested
    • PLK2 phosphorylation sites on SynGAP not fully mapped
  14. 2019 Medium

    A non-synaptic interaction with dopamine D1 receptors in prenatal brain was discovered: SynGAP facilitates D1R surface localization and signaling required for tangential migration of GABAergic interneurons, expanding SynGAP's functional repertoire beyond postsynaptic signaling.

    Evidence Co-immunoprecipitation from prenatal brain, TAT-peptide disruption, and in vivo interneuron migration assay

    PMID:31387938

    Open questions at the time
    • Single lab observation without independent replication
    • Whether D1R interaction is direct or scaffolded through intermediaries not resolved
  15. 2019 High

    Adult re-expression of SynGAP in haploinsufficient mice improved hippocampal oscillations, memory, and seizure phenotypes, demonstrating that SynGAP retains therapeutically relevant functions beyond the developmental critical period.

    Evidence Inducible gene restoration in adult mice, video-EEG, and behavioral memory tests

    PMID:31025938

    Open questions at the time
    • Degree of rescue relative to developmental restoration not quantitatively compared
    • Which adult functions are GAP-dependent versus scaffold-dependent unknown
  16. 2020 High

    The phase separation hypothesis was functionally validated: SynGAP-α1 undergoes LLPS with PSD-95 to regulate LTP, while β isoform (lacking PDZ binding) instead promotes dendritic arborization; a phase-separation-disrupting mutation converts α1 to β-like function, establishing LLPS as the mechanistic basis for isoform-specific synaptic versus morphological roles.

    Evidence Isoform-specific expression, in vitro LLPS assays, mutagenesis, LTP recordings, and dendritic morphology analysis in mouse neurons

    PMID:32068252 PMID:32579114

    Open questions at the time
    • In vivo phase separation dynamics at single-synapse resolution not directly observed
    • Mechanism by which β promotes dendritic arborization not identified
  17. 2020 High

    SynGAP was shown to regulate synaptic strength by physically competing with AMPAR–TARP complexes for PSD-95 condensate occupancy, independently of GAP catalytic activity; GAP-inactivating knock-in mice retained normal LTP and behavior, establishing the structural/scaffolding role as separable from catalysis.

    Evidence GAP-domain inactivating knock-in mouse, synaptic plasticity recordings, behavioral testing, molecular condensate assays

    PMID:38422154

    Open questions at the time
    • How structural competition and catalytic activity are coordinately deployed across different forms of plasticity remains unresolved
  18. 2022 High

    O-GlcNAcylation at T1306 was identified as a novel post-translational mechanism that suppresses SynGAP/PSD-95 phase separation in a dominant-negative manner, adding a metabolic/nutrient-sensing layer to LLPS regulation.

    Evidence Protein semisynthesis for site-specific O-GlcNAcylation, in vitro and cell-based LLPS assays, mass spectrometry from rat brain

    PMID:35637289

    Open questions at the time
    • In vivo physiological conditions regulating O-GlcNAcylation of SynGAP not defined
    • Interplay between O-GlcNAcylation and CaMKII phosphorylation not tested
  19. 2022 Medium

    ROCK was identified as a fourth kinase regulating SynGAP, phosphorylating Ser842 to promote 14-3-3ζ binding, PSD-95 dissociation, and Ras-ERK activation during LTP, broadening the kinase network controlling SynGAP synaptic dynamics.

    Evidence In vitro kinase assay, ROCK inhibitor in neurons, co-immunoprecipitation, NMDA/glycine LTP stimulation

    PMID:35624196

    Open questions at the time
    • Single lab without independent replication
    • Relative contribution of ROCK versus CaMKII to SynGAP dispersion in vivo not determined
  20. 2023 High

    A post-transcriptional regulatory mechanism was defined: PTBP1/2 promote an alternative 3' splice site in SYNGAP1 that triggers NMD; genetic deletion of this splice site or antisense oligonucleotides that block PTBP binding upregulate SynGAP protein and rescue electrophysiological deficits in haploinsufficient models, providing a therapeutic strategy.

    Evidence CLIP-seq, minigene assays, ASO treatment of human iPSC-neurons, and genetic A3SS deletion in mice with LTP and excitability recordings

    PMID:36917980 PMID:37149717

    Open questions at the time
    • Long-term in vivo efficacy and safety of ASO approach not established
    • Whether NMD isoform has any functional role beyond degradation unknown
  21. 2023 High

    Non-synaptic developmental functions were discovered: SYNGAP1 is expressed in human radial glia where it regulates cytoskeletal dynamics, division plane, and cortical lamination, demonstrating that disease pathology extends beyond synaptic dysfunction to neurogenesis.

    Evidence CRISPR SYNGAP1 KO in human cortical organoids, immunostaining, live imaging of RGC division, validated in mouse model

    PMID:37946050

    Open questions at the time
    • Molecular targets of SynGAP in radial glia cytoskeleton not identified
    • Whether radial glia phenotype involves GAP activity or scaffolding function unknown
  22. 2024 High

    The catalytic versus structural function debate was resolved for seizures: GAP-inactivating knock-in mice recapitulate intrinsic excitability deficits but not seizure susceptibility, establishing that the scaffolding/competition role—not catalysis—is the principal mechanism underlying epilepsy in SYNGAP1 haploinsufficiency.

    Evidence GAP domain knock-in mutant mice, whole-cell patch clamp, PTZ seizure assay, video-EEG

    PMID:40294267

    Open questions at the time
    • Which specific scaffolding interactions are seizure-relevant not identified
    • Whether this dissociation holds for other SYNGAP1 disease phenotypes unknown
  23. 2024 High

    SYNGAP1 was shown to control the species-specific tempo of human synaptogenesis (synaptic neoteny) through epistatic interaction with the human-specific SRGAP2B/C paralogs, which increase postsynaptic SynGAP1 levels by antagonizing SRGAP2A; loss of SYNGAP1 abolishes this neotenic program.

    Evidence Xenotransplantation of CRISPR SYNGAP1 KO human neurons into mouse brain, combinatorial KD of SRGAP2B/C and SYNGAP1, in vivo two-photon imaging and electrophysiology

    PMID:39111306 PMID:39406239

    Open questions at the time
    • Direct physical interaction between SRGAP2A and SynGAP1 not demonstrated
    • Whether this epistasis operates in non-cortical brain regions is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include: what is the full-length structure of SynGAP and how do post-translational modifications coordinately regulate its phase separation, catalytic activity, and scaffolding competition in vivo; how SynGAP's non-synaptic functions in radial glia contribute quantitatively to disease; and whether ASO-mediated upregulation can rescue established circuit-level deficits in patients.
  • No full-length SynGAP structure available
  • Quantitative contribution of radial glia versus synaptic mechanisms to SYNGAP1 encephalopathy undefined
  • In vivo ASO efficacy and therapeutic window in patients untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 3 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-112316 Neuronal System 4 R-HSA-1266738 Developmental Biology 4 R-HSA-8953854 Metabolism of RNA 2
Partners
CAMK2ACDK5DLG2DLG3DLG4MPDZPLK2YWHAZ
Complex memberships
MUPP1-SynGAP-CaMKII complexPSD-95/NMDAR postsynaptic density complexSynGAP-PSD-95 phase-separated condensate

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 SynGAP is a Ras-GTPase activating protein that physically associates with the PDZ domains of PSD-95 and SAP102 in vitro and in vivo, forming a large macromolecular complex with PSD-95 and the NMDA receptor at excitatory synapses, and stimulates the GTPase activity of Ras. Co-immunoprecipitation, GST pulldown (PDZ domain interaction), in vitro GTPase activity assay, subcellular fractionation/immunostaining Neuron High 9581761
1998 p135 SynGAP Ras-GTPase activating activity is inhibited by phosphorylation by CaMKII, predicting that CaMKII activation stops inactivation of GTP-bound Ras, potentially activating the MAP kinase pathway upon NMDA receptor activation. In vitro kinase assay, GTPase activity assay, immunostaining/colocalization with PSD-95 and NMDA receptors Neuron High 9620694
2002 SynGAP regulates ERK/MAPK signaling and is required for LTP induction in hippocampal CA1; basal levels of activated ERK2 are elevated in SynGAP heterozygous null mice, and SynGAP lies downstream of NMDA receptors and PSD-95 in regulating synaptic plasticity and spatial learning. Heterozygous null mouse genetic model, hippocampal LTP recordings, ERK2 phosphorylation biochemistry, behavioral spatial learning tests The Journal of neuroscience High 12427827
2004 SynGAP is present in a complex with MUPP1 (a multi-PDZ protein) and CaMKII at hippocampal synapses; Ca2+/CaM binding to CaMKII dissociates it from the MUPP1-SynGAP complex; SynGAP dephosphorylation in this context activates p38 MAPK, potentiates synaptic AMPA responses, and increases AMPAR-containing clusters. Co-immunoprecipitation, peptide disruption of complex, siRNA knockdown, electrophysiology (synaptic AMPA responses), imaging of AMPAR clusters Neuron High 15312654
2004 Phosphorylation of SynGAP by CaMKII increases its Ras GTPase-activating activity by 70-95%; four major phosphorylation sites in the C-terminal tail (Ser1123, Ser1058, Ser750/751/756, Ser764/765) are identified; phosphorylation at Ser765 and Ser1123 is increased in cortical neurons after NMDA stimulation. In vitro kinase assay with recombinant synGAP, mass spectrometry site identification, mutagenesis of phosphosites, phospho-specific antibodies, GTPase activity assay in neurons The Journal of biological chemistry High 14970204
2004 Spine and synapse formation are accelerated in SynGAP knockout neurons; the GAP domain activity and C-terminal PSD-95 binding domain of SynGAP are both required for normal regulation of spine and synapse formation, as demonstrated by rescue experiments with wild-type versus mutant SynGAP constructs. SynGAP homozygous KO neurons in culture, biolistic transfection rescue with wild-type and GAP-domain or PDZ-binding mutants, morphological and electrophysiological analysis The Journal of neuroscience High 15470153
2006 SynGAP regulates AMPA receptor trafficking and silent synapse number at excitatory synapses: overexpression depresses AMPAR-mediated mEPSCs and reduces synaptic AMPAR surface expression and insertion; loss of SynGAP increases synaptic transmission. SynGAP also bi-directionally regulates ERK and p38 MAPK signaling. SynGAP overexpression and siRNA knockdown in neurons, SynGAP KO mice, electrophysiology (mEPSC recordings), surface AMPAR immunostaining, kinase activity assays Proceedings of the National Academy of Sciences of the United States of America High 16537406
2008 The C2 domain of SynGAP is essential for RapGAP activity: the isolated GAP domain shows no detectable RapGAP activity, but a C2-GAP fragment stimulates Rap GTPase reaction ~10^4-fold; crystal structure of C2-GAP reveals a concerted movement of C2 domain toward switch II region of Rap to assist GTPase stimulation via a mechanism similar to canonical RasGAPs. Crystal structure of C2-GAP fragment, in vitro GTPase assay, domain truncation biochemistry, structural modeling EMBO reports High 18323856
2008 SynGAP is a key regulator of Rac-GTP and Ras-GTP levels and cofilin phosphorylation in adult mice; heterozygous deletion of synGAP elevates both Ras-GTP and Rac-GTP in forebrain, increases steady-state cofilin phosphorylation (promoting excess mushroom spines), and disrupts NMDA-induced transient cofilin dephosphorylation required for synaptic depression. SynGAP heterozygous KO mice, GTPase pull-down assays (Ras-GTP, Rac-GTP), phospho-cofilin western blotting, NMDA treatment of cultured neurons, LTD electrophysiology in slices The Journal of neuroscience High 19074040
2011 SynGAP moves out of the PSD core upon depolarization or NMDA application in hippocampal neurons, as shown by immunogold electron microscopy; this redistribution is reversible and occurs without PSD-95 redistribution, potentially freeing PSD core sites for other proteins such as TARPs. Immunogold electron microscopy of rat hippocampal neuronal cultures under basal and depolarizing/NMDA conditions Neuroscience Medium 21736925
2012 Pathogenic SYNGAP1 mutations cause premature dendritic spine maturation during the early postnatal critical period, dramatically enhancing hippocampal excitability and behavioral abnormalities; SynGAP acts as a developmental repressor of neural excitability that promotes life-long cognitive development. SYNGAP1 heterozygous KO mouse model, dendritic spine morphology analysis, hippocampal excitability recordings, behavioral tests, temporal genetic manipulation (induction after/before critical period) Cell High 23141534
2012 SynGAP-α1 and SynGAP-α2 C-terminal splice isoforms have opposing effects on synaptic strength: α1 overexpression decreases mEPSC amplitude/frequency while α2 increases them; the magnitude of this effect is modulated by the N-terminal sequence arising from alternative promoter usage. Overexpression of specific isoforms in hippocampal neurons, electrophysiology (mEPSC recordings), 5'RACE and primer extension to identify N-terminal variants Nature communications High 22692543
2013 SynGAP regulates protein synthesis in cortical neurons through ERK, mTOR, and Rheb; GluN2B-containing NMDARs and CaMKII act upstream of SynGAP in a signaling cascade required for translation-dependent homeostatic synaptic plasticity of excitatory synapses. SynGAP knockdown/KO in cortical neuron cultures, protein synthesis assays, pharmacological inhibitors of ERK/mTOR/Rheb, electrophysiology for homeostatic plasticity PloS one Medium 24391850
2014 Phosphorylation of recombinant SynGAP by CaMKII increases HRas GAP activity by 25% and Rap1 GAP activity by 76%; phosphorylation by CDK5 increases HRas GAP activity by 98% and Rap1 GAP activity by 20%; thus the two kinases differentially shift the ratio of SynGAP's GAP activity toward Ras versus Rap. CDK5 primarily phosphorylates Ser773 and Ser802. Both phosphorylation events are regulated by NMDA receptor activation in neurons. In vitro kinase assay with recombinant SynGAP, mass spectrometry phosphosite identification, mutagenesis, GTPase activity assays for HRas/Rap1/Rap2, phospho-specific detection in neurons after NMDA treatment The Journal of biological chemistry High 25533468
2015 CaMKII phosphorylation of SynGAP during LTP induction causes rapid dispersion of SynGAP from dendritic spines, which triggers Ras activation, AMPA receptor synaptic incorporation, and spine enlargement; the degree of acute SynGAP dispersion predicts the maintenance of spine enlargement. Live-cell imaging of fluorescently tagged SynGAP in hippocampal neurons during LTP induction, pharmacological inhibition of CaMKII, AMPAR trafficking assays Neuron High 25569349
2016 SynGAP-α1, by binding all three PDZ domains of PSD-95, can occupy ~15% of PDZ domains and restricts binding of other postsynaptic signaling proteins. Phosphorylation by CaMKII and PLK2 decreases SynGAP-α1 affinity for PDZ domains severalfold, freeing these domains for other proteins; heterozygous deletion of SynGAP increases levels of critical PSD proteins that bind PSD-95. Binding affinity measurements (ITC/biochemical), CaMKII/PLK2 in vitro phosphorylation and affinity assays, quantitative proteomics of PSDs from Syngap1 heterozygous mice eLife High 27623146
2017 SynGAP-α1 undergoes liquid-liquid phase separation with PSD-95 to form membraneless condensates at synapses, providing a mechanism for high-concentration synaptic anchoring; CaMKII-dependent phosphorylation modulates this phase separation and SynGAP's rapid activity-dependent dispersion from the PSD. In vitro phase separation assay, fluorescence microscopy of condensates, biochemical analysis Small GTPases Medium 28524815
2018 Polo-like kinase 2 (Plk2) phosphorylates SynGAP and stimulates its GAP activity toward HRas by 65% and toward Rap1 by 16%; simultaneous phosphorylation by Plk2 and CDK5 produces additive increases in HRas GAP activity (~230%) and also increases Rap2 GAP activity (~40-50%), an effect not produced by either kinase alone. In vitro kinase assay with recombinant SynGAP and Plk2/CDK5, GTPase activity assays for HRas/Rap1/Rap2, mass spectrometry phosphosite identification Biochemical and biophysical research communications High 30049443
2019 SynGAP interacts with the dopamine D1 receptor (D1R) in prenatal mouse brain tissue; this interaction facilitates D1R localization to the plasma membrane and promotes D1R-mediated PKA and p38 MAPK phosphorylation; disrupting the D1R-SynGAP interaction impairs tangential migration of GABAergic interneurons by altering actin and microtubule dynamics. Co-immunoprecipitation from prenatal brain tissue, peptide disruption (TAT-D1Rpep), in vivo interneuron migration assay, kinase phosphorylation assays Science signaling Medium 31387938
2020 SynGAP isoforms have distinct spatiotemporal expression and subcellular localization: α1 isoforms are always enriched in the PSD, α2 isoforms shift from non-synaptic to mostly PSD localization with age, and β isoforms are always enriched in non-synaptic locations. Isoform-specific antibodies, subcellular fractionation, western blotting across developmental time points in multiple brain regions, mouse and human samples Journal of neurochemistry Medium 32068252
2020 SynGAP-α1 undergoes liquid-liquid phase separation with PSD-95 and is highly synaptically enriched, which is required for LTP; SynGAP-β, which lacks PDZ-binding motif, is less synaptically targeted and instead promotes dendritic arborization. A mutation disrupting SynGAP-α1 phase separation abolishes LTP regulation and causes it to drive dendritic development like SynGAP-β. Isoform-specific expression in mouse neurons, LTP recordings, in vitro phase separation assays, mutagenesis of phase-separation domain, dendritic morphology analysis eLife High 32579114
2020 SynGAP modulates synaptic strength by physically competing with the AMPA-receptor-TARP excitatory receptor complex in the formation of molecular condensates with synaptic scaffolding proteins, independently of its GAP catalytic activity; inactivating mutations within the GAP domain do not inhibit synaptic plasticity or cause behavioral deficits. GAP-domain inactivating knock-in mouse model, synaptic plasticity recordings (LTP), behavioral testing, molecular condensate assays Science High 38422154
2020 In PSD fractions from Syngap1 heterozygous mice, the ratio of TARP (transmembrane AMPA receptor-associated proteins) to PSD-95 is increased, with a sex-specific difference: only females show a highly significant correlation between increased TARP and decreased SynGAP levels, revealing a sex-dependent adaptation of the PSD scaffold. Quantitative proteomics/western blotting of PSD fractions from male and female heterozygous Syngap1 mice eLife Medium 31939740
2013 CaMKII activation promotes removal of both SynGAP-α1 and SynGAP-α2 isoforms from the PSD core following NMDA stimulation, as shown by immunogold electron microscopy; CaMKII inhibitor tatCN21 blocks NMDA-induced redistribution of both isoforms. Immunogold electron microscopy, isoform-specific antibodies, CaMKII inhibitor (tatCN21), NMDA stimulation of hippocampal neuronal cultures PloS one Medium 23967245
2022 O-GlcNAcylation of SynGAP at T1306 suppresses liquid-liquid phase separation of the SynGAP/PSD-95 complex by blocking SynGAP interaction with PSD-95; O-GlcNAcylation acts in a dominant-negative manner enabling sub-stoichiometric modification to regulate LLPS; this modification is reversibly regulated by OGT and OGA. Protein semisynthesis to generate site-specifically O-GlcNAcylated SynGAP, in vitro and cell-based LLPS assays, identification of O-GlcNAc sites from rat brain endogenous SynGAP by mass spectrometry Nature chemistry High 35637289
2020 PSD-93 interacts with SynGAP and mediates its ubiquitination and proteasomal degradation following ischemic brain injury; the SynGAP 670-685 amino acid sequence is essential for binding PSD-93; NMDA receptor activation promotes this degradation pathway. Co-immunoprecipitation, proteasome inhibitor (MG-132) treatment, PSD-93 knockout mice, domain mapping with peptide disruption (Tat-SynGAP 670-685aa) Translational stroke research Medium 32130656
2001 SynGAP-β isoform, which lacks the C-terminal PSD-95-binding motif, does not interact with PSD-95 but specifically interacts with the non-phosphorylated α-subunit of CaMKII through its unique C-terminal tail; at least five protein isoforms exist from alternative splicing of the 3' region. cDNA cloning and sequencing, co-immunoprecipitation to test interactions with PSD-95 and CaMKII, subcellular fractionation The Journal of biological chemistry Medium 11278737
2001 Transient cerebral ischemia increases tyrosine phosphorylation of SynGAP; SynGAP binds SH2 domains of Src and Fyn in a tyrosine phosphorylation-dependent manner, and this interaction increases after ischemia; after ischemia, co-immunoprecipitation of SynGAP with PSD-95 decreases. Four-vessel occlusion rat model, western blotting with phospho-specific antibodies, SH2 domain pulldown assays, co-immunoprecipitation Journal of cerebral blood flow and metabolism Medium 11487731
2005 SynGAP plays a role in regulation of neuronal apoptosis; reduction of SynGAP below ~40% of wild-type levels causes cell-autonomous enhancement of caspase-3-mediated apoptosis in hippocampal and cortical neurons, with the level of apoptosis inversely correlating with SynGAP protein level. Conditional cre/loxP knockout mice with graded SynGAP reduction, caspase-3 immunostaining as apoptosis marker, cell-type-specific analysis The European journal of neuroscience Medium 15733080
2016 Syngap1 haploinsufficiency in GABAergic cells derived from the medial ganglionic eminence impairs their connectivity in a cell-autonomous manner, reduces perisomatic innervation by parvalbumin-positive basket cells, reduces inhibitory synaptic activity and cortical gamma oscillation power, and causes cognitive deficits. Cell-type specific Syngap1 conditional knockout, immunohistochemistry for PV basket cells, inhibitory synapse electrophysiology, EEG gamma oscillation recording, behavioral tests Nature communications High 27827368
2022 Rho-kinase (ROCK) phosphorylates SynGAP1 at Ser842, increasing its interaction with 14-3-3ζ and activating Ras-ERK signaling; this phosphorylation also promotes SynGAP1 dissociation from PSD-95 and delocalization from spines during NMDA-induced LTP. In vitro kinase assay, reconstitution in HeLa cells, Rho-kinase inhibitor in striatal neurons, NMDA/glycine LTP stimulation, co-immunoprecipitation, spine morphology imaging Neurochemical research Medium 35624196
2023 PTBP1/2 directly bind SYNGAP1 mRNA and promote alternative 3' splice site inclusion that induces nonsense-mediated mRNA decay; antisense oligonucleotides disrupting PTBP binding redirect splicing and increase SYNGAP1 mRNA and protein expression in human iPSC-derived neurons. PTBP2 CLIP-seq in human brain and iPSC-neurons, minigene splicing assays, antisense oligonucleotide treatment, RT-PCR, western blotting in SYNGAP1 haploinsufficient iPSC-neurons Nature communications High 37149717
2023 PTBP1/2 promote a Syngap1 alternative 3' splice site causing nonsense-mediated mRNA decay; genetic deletion of the Syngap1 A3SS in mice upregulates Syngap1 protein and alleviates LTP and membrane excitability deficits caused by a heterozygous Syngap1 knockout allele. Genetic deletion of A3SS in mice, electrophysiology (LTP, intrinsic excitability), RT-PCR isoform quantification, splice-switching oligonucleotide in human iPSC-neurons Neuron High 36917980
2023 SYNGAP1 is expressed in the apical domain of human radial glia cells (hRGCs) and regulates cytoskeletal dynamics, scaffolding and division plane of hRGCs; SYNGAP1 haploinsufficiency disrupts cortical lamination and accelerates maturation of cortical projection neurons in human cortical organoids, demonstrating non-synaptic functions in neurogenesis. Human cortical organoid model of SYNGAP1 haploinsufficiency (CRISPR), immunostaining for RGC markers, live imaging of cell division, cortical layer analysis, mouse model validation Nature neuroscience High 37946050
2024 Intrinsic excitability deficits (reduced input resistance, increased rheobase) in cortical excitatory neurons from Syngap1 heterozygous KO mice are recapitulated by GAP-deficient Syngap1 mutants; however, seizure severity and PTZ-induced seizure susceptibility are not affected by GAP-inactivating mutations, implicating the structural (non-catalytic) role of SynGAP in seizure regulation. GAP domain knock-in mutant mice, whole-cell patch clamp recordings (intrinsic excitability), PTZ seizure susceptibility assay, video-EEG Proceedings of the National Academy of Sciences of the United States of America High 40294267
2024 SYNGAP1-deficient human cortical neurons xenotransplanted into mouse brain display cell-autonomous acceleration of synaptic formation and maturation, disrupted synaptic plasticity, and precocious responsiveness to visual stimulation, demonstrating that SYNGAP1 is required for human neuronal synaptic neoteny. Xenotransplantation of CRISPR SYNGAP1 KO human cortical neurons into mouse brain, in vivo two-photon imaging, in vivo electrophysiology, morphological analysis Neuron High 39111306
2024 The tempo of synaptogenesis is set by reciprocal antagonism between SRGAP2A and SYNGAP1 at postsynaptic sites; human-specific SRGAP2B/C genes promote neoteny by reducing synaptic SRGAP2A, which in turn increases postsynaptic SYNGAP1 accumulation; combinatorial loss-of-function in vivo reveals this epistatic relationship. Xenotransplantation of human cortical neurons with combinatorial KD of SRGAP2B/C and SYNGAP1 in vivo, synaptic protein quantification, morphological and electrophysiological analysis Neuron High 39406239
2023 FMRP interacts with and regulates the translation of Syngap1 mRNA; reduced FMRP expression in Syngap1+/- mice during development leads to increased Syngap1 translation as a compensatory mechanism; these developmental changes alter eEF2 phosphorylation downstream of NMDAR-mediated signaling. Co-immunoprecipitation of FMRP with Syngap1 mRNA, polysome profiling, western blotting for FMRP and SynGAP across development in Syngap1+/- mice, eEF2 phosphorylation assays Frontiers in molecular neuroscience Medium 31143100
2019 Adult re-expression of SynGAP protein in a mouse model of SYNGAP1 haploinsufficiency improves electrophysiological measures of memory (hippocampal oscillations) and reduces seizures including interictal events that worsen during sleep, demonstrating that SynGAP retains therapeutically relevant biological functions in adulthood. Inducible gene restoration in adult Syngap1 haploinsufficient mice, video-EEG for seizure and interictal event monitoring, behavioral memory tests eLife High 31025938

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family. Neuron 539 9581761
1998 A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II. Neuron 498 9620694
2012 Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses. Cell 296 23141534
2002 SynGAP regulates ERK/MAPK signaling, synaptic plasticity, and learning in the complex with postsynaptic density 95 and NMDA receptor. The Journal of neuroscience : the official journal of the Society for Neuroscience 279 12427827
2009 Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation. The New England journal of medicine 269 19196676
2004 SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation. Neuron 237 15312654
2015 Rapid dispersion of SynGAP from synaptic spines triggers AMPA receptor insertion and spine enlargement during LTP. Neuron 225 25569349
2006 SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons. Proceedings of the National Academy of Sciences of the United States of America 207 16537406
2012 Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency. Human mutation 206 23161826
2004 SynGAP regulates spine formation. The Journal of neuroscience : the official journal of the Society for Neuroscience 159 15470153
2018 SYNGAP1 encephalopathy: A distinctive generalized developmental and epileptic encephalopathy. Neurology 156 30541864
2011 De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism. Biological psychiatry 143 21237447
2016 Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy. Journal of medical genetics 140 26989088
2020 Twenty Years of SynGAP Research: From Synapses to Cognition. The Journal of neuroscience : the official journal of the Society for Neuroscience 117 32075947
2008 SynGAP regulates steady-state and activity-dependent phosphorylation of cofilin. The Journal of neuroscience : the official journal of the Society for Neuroscience 103 19074040
2004 Regulation of the neuron-specific Ras GTPase-activating protein, synGAP, by Ca2+/calmodulin-dependent protein kinase II. The Journal of biological chemistry 103 14970204
2009 Reduced expression of the NMDA receptor-interacting protein SynGAP causes behavioral abnormalities that model symptoms of Schizophrenia. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 99 19145222
2014 Syngap1 haploinsufficiency damages a postnatal critical period of pyramidal cell structural maturation linked to cortical circuit assembly. Biological psychiatry 95 25444158
2016 SYNGAP1: Mind the Gap. Frontiers in cellular neuroscience 92 26912996
2015 De novo, heterozygous, loss-of-function mutations in SYNGAP1 cause a syndromic form of intellectual disability. American journal of medical genetics. Part A 87 26079862
2008 The C2 domain of SynGAP is essential for stimulation of the Rap GTPase reaction. EMBO reports 86 18323856
2020 SynGAP isoforms differentially regulate synaptic plasticity and dendritic development. eLife 79 32579114
2018 Species-conserved SYNGAP1 phenotypes associated with neurodevelopmental disorders. Molecular and cellular neurosciences 73 29580901
2016 A model for regulation by SynGAP-α1 of binding of synaptic proteins to PDZ-domain 'Slots' in the postsynaptic density. eLife 72 27623146
2012 SynGAP isoforms exert opposing effects on synaptic strength. Nature communications 72 22692543
2016 Decrease of SYNGAP1 in GABAergic cells impairs inhibitory synapse connectivity, synaptic inhibition and cognitive function. Nature communications 70 27827368
2019 Re-expression of SynGAP protein in adulthood improves translatable measures of brain function and behavior. eLife 69 31025938
2019 Comprehensive behavioral analysis of heterozygous Syngap1 knockout mice. Neuropsychopharmacology reports 69 31323176
2015 Convergence of Hippocampal Pathophysiology in Syngap+/- and Fmr1-/y Mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 67 26558778
2017 3'UTR Length-Dependent Control of SynGAP Isoform α2 mRNA by FUS and ELAV-like Proteins Promotes Dendritic Spine Maturation and Cognitive Function. Cell reports 65 28954225
2014 Phosphorylation of synaptic GTPase-activating protein (synGAP) by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclin-dependent kinase 5 (CDK5) alters the ratio of its GAP activity toward Ras and Rap GTPases. The Journal of biological chemistry 65 25533468
2013 SynGAP regulates protein synthesis and homeostatic synaptic plasticity in developing cortical networks. PloS one 65 24391850
2015 Two knockdown models of the autism genes SYNGAP1 and SHANK3 in zebrafish produce similar behavioral phenotypes associated with embryonic disruptions of brain morphogenesis. Human molecular genetics 63 25882707
2010 Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP. The European journal of neuroscience 63 20105235
2024 SynGAP regulates synaptic plasticity and cognition independently of its catalytic activity. Science (New York, N.Y.) 60 38422154
2022 O-GlcNAcylation modulates liquid-liquid phase separation of SynGAP/PSD-95. Nature chemistry 60 35637289
2023 Non-synaptic function of the autism spectrum disorder-associated gene SYNGAP1 in cortical neurogenesis. Nature neuroscience 54 37946050
2020 SYNGAP1 Controls the Maturation of Dendrites, Synaptic Function, and Network Activity in Developing Human Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 53 32887745
2019 Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and developmental progression. Journal of neurodevelopmental disorders 52 31395010
2019 SYNGAP1 mutations: Clinical, genetic, and pathophysiological features. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 52 31454529
2001 Characterization of a novel synGAP isoform, synGAP-beta. The Journal of biological chemistry 52 11278737
2023 Upregulation of SYNGAP1 expression in mice and human neurons by redirecting alternative splicing. Neuron 46 36917980
2020 Low-Dose Perampanel Rescues Cortical Gamma Dysregulation Associated With Parvalbumin Interneuron GluA2 Upregulation in Epileptic Syngap1+/- Mice. Biological psychiatry 44 32107006
2005 Differential expression of two NMDA receptor interacting proteins, PSD-95 and SynGAP during mouse development. The European journal of neuroscience 44 15673435
2011 SynGAP moves out of the core of the postsynaptic density upon depolarization. Neuroscience 40 21736925
2005 A role for synGAP in regulating neuronal apoptosis. The European journal of neuroscience 40 15733080
2020 SynGAP splice variants display heterogeneous spatio-temporal expression and subcellular distribution in the developing mammalian brain. Journal of neurochemistry 39 32068252
2018 The first international conference on SYNGAP1-related brain disorders: a stakeholder meeting of families, researchers, clinicians, and regulators. Journal of neurodevelopmental disorders 39 29402231
2013 Camkii-mediated phosphorylation regulates distributions of Syngap-α1 and -α2 at the postsynaptic density. PloS one 31 23967245
2018 Chewing induced reflex seizures ("eating epilepsy") and eye closure sensitivity as a common feature in pediatric patients with SYNGAP1 mutations: Review of literature and report of 8 cases. Seizure 30 30685520
2011 A balanced translocation disrupts SYNGAP1 in a patient with intellectual disability, speech impairment, and epilepsy with myoclonic absences (EMA). Epilepsia 27 22050443
2020 PSD-93 Interacts with SynGAP and Promotes SynGAP Ubiquitination and Ischemic Brain Injury in Mice. Translational stroke research 26 32130656
2004 Impaired SynGAP expression and long-term spatial learning and memory in hippocampal CA1 area from rats previously exposed to perinatal hypoxia-induced insults: beneficial effects of A68930. Neuroscience letters 26 15500970
2022 Clinical and behavioural features of SYNGAP1-related intellectual disability: a parent and caregiver description. Journal of neurodevelopmental disorders 24 35655128
2013 6p21.3 microdeletion involving the SYNGAP1 gene in a patient with intellectual disability, seizures, and severe speech impairment. American journal of medical genetics. Part A 24 23687080
2023 Mapping PTBP2 binding in human brain identifies SYNGAP1 as a target for therapeutic splice switching. Nature communications 23 37149717
2017 Analysis of 31-year-old patient with SYNGAP1 gene defect points to importance of variants in broader splice regions and reveals developmental trajectory of SYNGAP1-associated phenotype: case report. BMC medical genetics 22 28576131
2012 Molecular and behavioral changes associated with adult hippocampus-specific SynGAP1 knockout. Learning & memory (Cold Spring Harbor, N.Y.) 22 22700469
2020 Learning and reaction times in mouse touchscreen tests are differentially impacted by mutations in genes encoding postsynaptic interacting proteins SYNGAP1, NLGN3, DLGAP1, DLGAP2 and SHANK2. Genes, brain, and behavior 20 33347690
2017 Anchoring high concentrations of SynGAP at postsynaptic densities via liquid-liquid phase separation. Small GTPases 20 28524815
2015 SYNGAP1 Mutation in Focal and Generalized Epilepsy: A Literature Overview and A Case Report with Special Aspects of the EEG. Neuropediatrics 20 26110312
2022 Sensory processing dysregulations as reliable translational biomarkers in SYNGAP1 haploinsufficiency. Brain : a journal of neurology 19 34791091
2018 Chronic treatment with a MEK inhibitor reverses enhanced excitatory field potentials in Syngap1+/- mice. Pharmacological reports : PR 19 29940508
2001 Transient cerebral ischemia increases tyrosine phosphorylation of the synaptic RAS-GTPase activating protein, SynGAP. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 19 11487731
2020 Pressure Sensitivity of SynGAP/PSD-95 Condensates as a Model for Postsynaptic Densities and Its Biophysical and Neurological Ramifications. Chemistry (Weinheim an der Bergstrasse, Germany) 18 31910298
2024 Comprehensive phenotypes of patients with SYNGAP1-related disorder reveals high rates of epilepsy and autism. Epilepsia 17 38470175
2022 Endogenous Syngap1 alpha splice forms promote cognitive function and seizure protection. eLife 17 35394425
2021 Phenotypes in Children With SYNGAP1 Encephalopathy in China. Frontiers in neuroscience 17 34924933
2019 Disruption of SynGAP-dopamine D1 receptor complexes alters actin and microtubule dynamics and impairs GABAergic interneuron migration. Science signaling 17 31387938
2023 Mouse models of SYNGAP1-related intellectual disability. Proceedings of the National Academy of Sciences of the United States of America 16 37669379
2019 Differential Regulation of Syngap1 Translation by FMRP Modulates eEF2 Mediated Response on NMDAR Activity. Frontiers in molecular neuroscience 16 31143100
2019 Tumor Suppression of Ras GTPase-Activating Protein RASA5 through Antagonizing Ras Signaling Perturbation in Carcinomas. iScience 16 31654850
2024 Accelerating therapeutic development and clinical trial readiness for STXBP1 and SYNGAP1 disorders. Current problems in pediatric and adolescent health care 14 38472035
2021 Experiential modulation of social dominance in a SYNGAP1 rat model of Autism Spectrum Disorders. The European journal of neuroscience 14 34672048
2020 A sex difference in the response of the rodent postsynaptic density to synGAP haploinsufficiency. eLife 14 31939740
2020 Multi-parametric analysis of 57 SYNGAP1 variants reveal impacts on GTPase signaling, localization, and protein stability. American journal of human genetics 14 33308442
2009 Appetitively motivated instrumental learning in SynGAP heterozygous knockout mice. Behavioral neuroscience 14 19824778
2023 Mnk1/2 kinases regulate memory and autism-related behaviours via Syngap1. Brain : a journal of neurology 13 36315645
2021 Syngap1 regulates experience-dependent cortical ensemble plasticity by promoting in vivo excitatory synapse strengthening. Proceedings of the National Academy of Sciences of the United States of America 13 34404727
2018 Phosphorylation of synaptic GTPase-activating protein (synGAP) by polo-like kinase (Plk2) alters the ratio of its GAP activity toward HRas, Rap1 and Rap2 GTPases. Biochemical and biophysical research communications 13 30049443
2003 Cerebral ischemia immediately increases serine phosphorylation of the synaptic RAS-GTPase activating protein SynGAP by calcium/calmodulin-dependent protein kinase II alpha in hippocampus of rats. Neuroscience letters 13 12951199
2024 SYNGAP1 deficiency disrupts synaptic neoteny in xenotransplanted human cortical neurons in vivo. Neuron 12 39111306
2024 Key roles of C2/GAP domains in SYNGAP1-related pathophysiology. Cell reports 12 39269903
2022 Abnormal brain state distribution and network connectivity in a SYNGAP1 rat model. Brain communications 12 36349120
2015 Wnt-related SynGAP1 is a neuroprotective factor of glutamatergic synapses against Aβ oligomers. Frontiers in cellular neuroscience 12 26124704
2025 Dissociation of SYNGAP1 enzymatic and structural roles: Intrinsic excitability and seizure susceptibility. Proceedings of the National Academy of Sciences of the United States of America 11 40294267
2024 Hyperexcitability and translational phenotypes in a preclinical mouse model of SYNGAP1-related intellectual disability. Translational psychiatry 11 39358332
2024 Synaptic neoteny of human cortical neurons requires species-specific balancing of SRGAP2-SYNGAP1 cross-inhibition. Neuron 11 39406239
2024 Haploinsufficiency of Syngap1 in Striatal Indirect Pathway Neurons Alters Motor and Goal-Directed Behaviors in Mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 10 39358043
2022 Effects of Cosolvents and Crowding Agents on the Stability and Phase Transition Kinetics of the SynGAP/PSD-95 Condensate Model of Postsynaptic Densities. The journal of physical chemistry. B 10 35171623
2021 Pharmacological intervention in young adolescents rescues synaptic physiology and behavioural deficits in Syngap1+/- mice. Experimental brain research 10 34739555
2011 Reduced expression of SynGAP, a neuronal GTPase-activating protein, enhances capsaicin-induced peripheral sensitization. Journal of neurophysiology 10 21525372
2008 Differential distribution of synGAP alpha1 and synGAP beta isoforms in rat neurons. Brain research 10 18824155
2024 SynGAP: a synteny-based toolkit for gene structure annotation polishing. Genome biology 9 39138517
2023 Case report: Off-label use of low-dose perampanel in a 25-month-old girl with a pathogenic SYNGAP1 variant. Frontiers in neurology 9 37662032
2004 PSD-95 promotes CaMKII-catalyzed serine phosphorylation of the synaptic RAS-GTPase activating protein SynGAP after transient brain ischemia in rat hippocampus. Brain research 9 15044063
2023 Interneuron-Targeted Disruption of SYNGAP1 Alters Sensory Representations in the Neocortex and Impairs Sensory Learning. The Journal of neuroscience : the official journal of the Society for Neuroscience 8 37558489
2022 Rho-Rho-Kinase Regulates Ras-ERK Signaling Through SynGAP1 for Dendritic Spine Morphology. Neurochemical research 8 35624196
2018 Clinical Transcriptome Sequencing Confirms Activation of a Cryptic Splice Site in Suspected SYNGAP1-Related Disorder. Molecular syndromology 8 30800045
2017 Pharmacoresistant epileptic eyelid twitching in a child with a mutation in SYNGAP1. Epileptic disorders : international epilepsy journal with videotape 8 28721930